IDH1 R132G

The Idylla IDH1-2 Mutation Assay Kit performed on the Biocartis Idylla system demonstrated a rapid and cost-effective alternative to the standard approaches. This assay can be used to evaluate clinically relevant IDH variants in a much shorter turnaround time and from limited biological samples, which makes this a preferred technique to develop clinical tests for diagnosis, prognosis, and evaluation of treatment in AML.

P2, N=14, Active, not recruiting, National Cancer Institute (NCI) | N=94 --> 14 | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Jan 2024

P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

No IDH2 mutations were found. The use of independent diagnostic methods may improve the detection of IDH-mutant specimens in chondroid tumors.

P3, N=220, Recruiting, Servier Affaires Médicales | Phase classification: P3b --> P3

P2, N=94, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Specifically, we found that ddPCR rescued hotspot mutations such as BRAF V600E (2/3, 66.7%), IDH1 R132G/H (3/8, 37.5%), TERT C228T (11/26, 42.3%), and TERT C250T (2/4, 50.0%). Collectively, our results suggest that a combined-modality approach involving MSK-IMPACTâ„¢ and ddPCR enables comprehensive assessment of limited CSF ctDNA samples with high sensitivity and provides a minimally invasive methodology to molecularly profiling glioma.

P2, N=94, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting

P2, N=94, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024

P3b, N=220, Recruiting, Servier

2HG-MRS demonstrated high sensitivity and specificity for the prediction of IDH-mutant BSG. In addition, 2HG-MRS may be useful for predicting the prognosis of adult BSG patients.

P2, N=94, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

The DNA methylation signature presented here has the potential to refine the utility of WGMA to predict IDH1/IDH2 mutation status of gliomas, thus improving diagnostic yield and efficiency of laboratory testing compared to single analyte IDH1/IDH2 or 1p19q tests.

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2022 --> Jul 2023 | Trial primary completion date: Jul 2022 --> Jul 2023

In recent years the US Food and Drug Administration (FDA) has been very active in approving targeted therapeutic drugs for AML patients including Midostaurin (Rydapt; 2017) and Gilteritinib (Xospata;2018) for FLT3 mutations; Enasidenib (Idhifa; 2017) for IDH2 mutations and Ivosidenib (Tibsovo; 2018) for IDH1 mutations. The IDH1 CDx, IDH2 CDx and FLT3 CDx tests are highly sensitive and Versiti provides average turn around time of 3 business days which enable rapid decision making on the recently available drug therapies for AML patients. We strongly recommend that the IDH1 CDx, IDH2 CDx and FLT3 CDx tests should be performed on all AML patients for better care.

In these AML patients, the persistence of IDH1/2 mutations may be part of a more complex process involving clonal hematopoiesis. In such setting, further studies on the biological and clinical significance of IDH1/2 mutations persistence are warranted.

CONCLUSIONS 2HG in adult brainstem glioma was detected by conventional 3T-MRS successfully. A noninvasive 2HG-MRS may be useful diagnostic modality for evaluating molecular status and prognosis in brainstem glioma noninvasively.

Responses were observed across IDH1 R132 mutation subtypes, with a relatively lower CR/CRh response rate for pts with a R132H mutation as compared to other subtypes. Pts with a best response of CR/CRh had fewer co-mutations than pts who did not achieve CR/CRh. While the ORR was not significantly reduced for pts with RTK mutations, these pts had a lower CR/CRh response rate compared to pts without any RTK mutations.

Here we report interim results of a Phase 2 study evaluating safety and efficacy of IVO in three different cohorts of MDS patients: Higher risk MDS having failed azacytidine (AZA) (cohort A, n=29), untreated higher risk MDS without life threatening cytopenias (ie ANC < 500/mm3 or any recent severe infections and/or platelets below 30,000/mm3 and any bleeding symptom,) as a first line treatment (cohort B, with the addition of AZA in non-Responders after 3 cycles, n=29) and lower risk MDS having failed EPO (cohort C, n=10). At data cut off (6/15/2021), 32 patients had been enrolled, including 26 who were evaluable for the primary endpoint. 13, 11 and 2 were enrolled in cohort A, B and C respectively. Median age was 76 years and 50% were female.

The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease...Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54 Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different IDH1 mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas.

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2021 --> Jul 2022 | Trial primary completion date: Jul 2021 --> Jul 2022

There is an emerging body of evidence that suggests these subtypes have different biochemical properties with prognostic significance, and with novel targetable agents, possible therapeutic implications. In addition, the association of PALB2 mutation in high grade gliomas is not well characterized, and in the setting of a rare IDH1 R132 subtype, has not previously been described.

IHC employing mAbs 14H7, 3C11, MMab1 can facilitate molecular diagnosis as a reliable, fast and inexpensive alternative for specific IDH2 variants detection. Given the distinct distribution of IDH2 R172 mutations in cancers, these mAbs could serve also as useful pathologic diagnostic markers.

Here we report new, molecularly defined subset of IDH1 mut IHCC, in keeping with the role of IDH1 as an oncogenic driver. Furthermore, our study identifies IDH1 R132 locus as the most frequent mutation (>99%), which may indicate sensitivity to anti- IDH1 targeted therapies such as ivosidenib, an FDA approved agent for treatment of a subset of IDH1 mutated acute myelogenous leukemias.

Ivosidenib and enasidenib, the IDH1 and IDH2 inhibitors, have been approved by the FDA for the treatment of adult relapsed or refractory (R/R) AML with IDH1 and IDH2 mutations, respectively. More than 70% of AML patients on IDH inhibitor therapies had detectable IDH mutations at the time of remission, indicating that IDH inhibitors induce blast differentiation/maturation rather than cell death. For AML patients with IDH2 mutations on enasidenib, the patients with R140Q mutations are more likely to have persistent mutation at the time of remission than those with R172K mutations.

P2, N=94, Recruiting, National Cancer Institute (NCI) | N=46 --> 94

The frequency and pattern of IDH mutations in CC are likely to vary among patients with different ethnicities. These findings suggest that characterization of the oncogenic mutation profile in different populations is of high clinical importance.

P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2020 --> Jul 2021 | Trial primary completion date: Jul 2020 --> Jul 2021

P2, N=46, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Dec 2022